Prevalence of latent structural heart disease in Nepali schoolchildren.

BACKGROUND: The present study aimed to quantify the burden of structural heart disease in Nepali children. METHODS: We performed a school-based cross-sectional echocardiographic screening study with cluster random sampling among children 5-16 years of age. RESULTS: Between December 2012 and January 2019, 6573 children (mean age 10.6 ± 2.9 years) from 41 randomly selected schools underwent echocardiographic screening. Structural heart disease was detected in 14.0 per 1000 children (95% CI 11.3-17.1) and was congenital in 3.3 per 1000 (95% CI 2.1-5.1) and rheumatic in 10.6 per 1000 (95% CI 8.3-13.4). Rates of rheumatic heart disease were higher among children attending public as compared to private schools (OR 2.8, 95% CI 1.6-5.2, p = 0.0001). CONCLUSION: Rheumatic heart disease accounted for three out of four cases of structural heart disease and was more common among children attending public as compared to private schools.

Chest Pain and Hemodynamic Instability in a Young Woman.

We report the case of an 18-year-old female admitted to the hospital for severe hemodynamic instability and fatal outcome within 6 hours following admission. Significant electrocardiographic modifications were noted and are presented with diagnostic options. (Level of Difficulty: Intermediate.).

Mid-term outcome of children with latent rheumatic heart disease in eastern Nepal.

INTRODUCTION: Systematic echocardiographic screening of children in regions with an endemic pattern of rheumatic heart disease allows for the early detection of valvular lesions suggestive of subclinical rheumatic heart disease. The natural course of latent rheumatic heart disease is, however, incompletely understood at this time. METHODS: We performed a prospective cohort study of children detected to have echocardiographic evidence of definite or borderline rheumatic heart disease according to the World Heart Federation Criteria. RESULTS: Among 53 children found to have definite (36) or borderline (17) rheumatic heart disease, 44 (83%) children underwent follow-up at a median of 1.9 years (IQR 1.1-4.5). The median age of the children was 11 years (IQR 9-14) and 34 (64.2%) were girls. Among children with definite rheumatic heart disease, 21 (58.3%) were adherent to secondary antibiotic prophylaxis, 7 (19.4%) were not, information on adherence was missing in 2 (5.6%) children and 6 (16.7%) were lost to follow-up. Regression of disease was observed in 10 children (27.8%), whereas 20 children (55.6%) had stable disease. Among children adherent to secondary prophylaxis, seven (33.3%) showed regression of disease. Among children with borderline disease, seven (41.2%) showed regression of disease, three (17.6%) progression of disease, four (23.5%) remained stable and three (17.6%) were lost to follow-up. On univariate analysis, we identified no predictors of disease regression, and no predictors for lost to follow-up or non-adherence with secondary antibiotic prophylaxis. CONCLUSION: Definite rheumatic heart disease showed regression in one in four children. Borderline disease was spontaneously reversible in less than half of the children and progressed to definite rheumatic heart disease in one in five children. TRIAL REGISTRATION NUMBER: NCT01550068.

Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions. Objective: To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease. Design, Setting, and Participants: This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019. Interventions: In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening. Main Outcomes and Measures: Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention. Results: A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008). Conclusions and Relevance: School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions. Trial Registration: ClinicalTrials.gov Identifier: NCT01550068.

Tailoring Midazolam-Loaded Chitosan Nanoparticulate Formulation for Enhanced Brain Delivery via Intranasal Route.

In the present study, midazolam (MDZ)-loaded chitosan nanoparticle formulation was investigated for enhanced transport to the brain through the intranasal (IN) route. These days, IN MDZ is very much in demand for treating life-threatening seizure emergencies; therefore, its nanoparticle formulation was formulated in the present work because it could substantially improve its brain targeting via the IN route. MDZ-loaded chitosan nanoparticles (MDZ-CSNPs) were formulated and optimized by the ionic gelation method and then evaluated for particle size, particle size distribution (PDI), drug loading (DL), encapsulation efficiency (EE), and in vitro release as well as in vitro permeation. The concentration of MDZ in the brain after the intranasal administration of MDZ-CSNPs (Cmax 423.41 ± 10.23 ng/mL, tmax 2 h, and area under the curve from 0 to 480 min (AUC0-480) of 1920.87 ng.min/mL) was found to be comparatively higher to that achieved following intravenous (IV) administration of MDZ solution (Cmax 245.44 ± 12.83 ng/mL, tmax 1 h, and AUC0-480 1208.94 ng.min/mL) and IN administration of MDZ solution (Cmax 211.67 ± 12.82, tmax 2 h, and AUC0-480 1036.78 ng.min/mL). The brain-blood ratio of MDZ-CSNPs (IN) were significantly greater at all sampling time points when compared to that of MDZ solution (IV) and MDZ (IN), which indicate that direct nose-to-brain delivery by bypassing the blood-brain barrier demonstrates superiority in brain delivery. The drug-targeting efficiency (DTE%) as well as nose-to-brain direct transport percentage (DTP%) of MDZ-CSNPs (IN) was found to be comparatively higher than that for other formulations, suggesting better brain targeting potential. Thus, the obtained results demonstrated that IN MDZ-CSNP has come up as a promising approach, which exhibits tremendous potential to mark a new landscape for the treatment of status epilepticus.

Prevalence of Subclinical Rheumatic Heart Disease in Eastern Nepal: A School-Based Cross-sectional Study.

IMPORTANCE: Although rheumatic heart disease has been nearly eradicated in high-income countries, 3 in 4 children grow up in parts of the world where it is still endemic. OBJECTIVES: To determine the prevalence of clinically silent and manifest rheumatic heart disease as a function of age, sex, and socioeconomic status and to estimate age-specific incidence. DESIGN, SETTING, AND PARTICIPANTS: In this school-based cross-sectional study with cluster sampling, 26 schools in the Sunsari district in Eastern Nepal with 5467 eligible children 5 to 15 years of age were randomly selected from 595 registered schools. After exclusion of 289 children, 5178 children were enrolled in the present study from December 12, 2012, through September 12, 2014. Data analysis was performed from October 1, 2014, to April 15, 2015. EXPOSURES: Demographic and socioeconomic characteristics were acquired in a standardized interview by means of a questionnaire customized to the age of the children. A focused medical history was followed by a brief physical examination. Cardiac auscultation and transthoracic echocardiography were performed by 2 independent physicians. MAIN OUTCOMES AND MEASURES: Rheumatic heart disease according to the World Heart Federation criteria. RESULTS: The median age of the 5178 children enrolled in the study was 10 years (interquartile range, 8-13 years), and 2503 (48.3%) were female. The prevalence of borderline or definite rheumatic heart disease was 10.2 (95% CI, 7.5-13.0) per 1000 children and increased with advancing age from 5.5 (95% CI, 3.5-7.5) per 1000 children 5 years of age to 16.0 (95% CI, 14.9-17.0) in children 15 years of age, whereas the mean incidence remained stable at 1.1 per 1000 children per year. Children with rheumatic heart disease were older than children without rheumatic heart disease (median age [interquartile range], 11 [9-14] years vs 10 [8-13] years; P = .03), more commonly female (34 [64.2%] vs 2469 [48.2%]; P = .02), and more frequently went to governmental schools (40 [75.5%] vs 2792 [54.5%]; P = .002). Silent disease (n = 44) was 5 times more common than manifest disease (n = 9). CONCLUSIONS AND RELEVANCE: Rheumatic heart disease affects 1 in 100 schoolchildren in Eastern Nepal, is primarily clinically silent, and may be more common among girls. The overall prevalence and the ratio of manifest to subclinical disease increase with advancing age, whereas the incidence remains stable at 1.1 per 1000 children per year. Early detection of silent disease may help prevent progression to severe valvular damage.

Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents.

BACKGROUND: Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age. METHODS: We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥ 5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data. FINDINGS: We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I² = 99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p = 0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p = 0·829).

Pregnancy complicated by heart disease in Nepal.

OBJECTIVE: To investigate the prevalence, characteristics and maternal and perinatal outcomes of pregnancies complicated by heart disease. DESIGN: Prospective single-centre registry. SETTING: Tertiary care teaching hospital in eastern Nepal. PATIENTS: Pregnant women presenting to the antenatal clinic and/or labour room between 1 March 2012 and 31 March 2013. MAIN OUTCOME MEASURES: Prevalence, characteristics, and maternal and perinatal outcomes of pregnancies complicated by heart disease. RESULTS: Fifty-three out of 9463 pregnancies (0.6%) were complicated by cardiac disease. Proportions of acquired, congenital and arrhythmic heart disease amounted to 89%, 9% and 2%, respectively. Rheumatic heart disease (RHD) was the most frequent cardiac disease complicating pregnancy (n=47). Among 45 women with RHD continuing pregnancy until delivery, 30 (67%) were primigravidae. The predominant valvular pathology was mitral stenosis (62%), followed by mitral regurgitation (21%) and aortic regurgitation (13%). Twenty women (44%) underwent elective or emergency caesarean section. Maternal and fetal/perinatal mortality of pregnancies complicated by RHD amounted to 4% and 16%, respectively. New York Heart Association (NYHA) functional class III or class IV (HR 6.0, 95% CI 1.2 to 29.1, p=0.026), pulmonary hypertension (HR 9.1, 95% CI 1.6 to 51.5, p=0.012) and severe mitral stenosis (HR 7.0, 95% CI 1.4 to 34.4, p=0.017) were identified as predictors of maternal or fetal/perinatal mortality in an univariate analysis. CONCLUSIONS: Rheumatic mitral stenosis was the most frequent heart disease complicating pregnancy in a consecutive cohort from a teaching hospital in Nepal. Exercise intolerance, pulmonary hypertension and severe mitral stenosis were identified as predictors of maternal or fetal/perinatal mortality.

An unusual culprit: simple angioplasty for a complex disease.

We present the case of an atypical presentation of myelofibrosis presenting with acute inferior-wall ST-elevation myocardial infarction. Besides cigarette smoking, the patient had no known traditional cardiovascular risk factors like diabetes, hypertension, or a sedentary lifestyle. He, however, had a hypercoagulable state due to a myeloproliferative neoplasm. This demonstrates that the typical presentation of a common emergency condition may involve more complex underlying illness, which when identified, may change the approach to the management of the patient for a more optimal outcome.

Rheumatic heart disease: pilot study for a population-based evaluation of prevalence and cardiovascular outcomes among schoolchildren in Nepal.

OBJECTIVES: To evaluate a protocol for a population-based programme targeting the prevention of rheumatic heart disease (RHD) progression by early echocardiographic diagnosis of valvular lesions and timely implementation of secondary prevention. DESIGN: Observational survey with a subsequent prospective cohort study. SETTING: Private boarding school in the urban area of the Sunsari district situated on the foothills of the Lower Himalayan Range in Eastern Nepal. PARTICIPANTS: Fifty-four unselected school-going children 5-15 years of age, 24 girls and 30 boys. PRIMARY OUTCOME MEASURE: Logistic feasibility of a large-scale population-based screening study using the echocardiographic criteria formulated by the World Heart Federation, with longitudinal follow-up of children with definite or borderline RHD in a prospective cohort study. RESULTS: Standardised interview, physical examination and screening echocardiography were performed in a three-staged process and took approximately 6 min per child. Socio-economic status was assessed using surrogate markers such as the occupation of the primary caregiver, numbers of rooms at home, car, television, cell phone and internet connection. Physical examination was focused on cardiac auscultation and signs of acute rheumatic fever and targeted echocardiography was performed by an independent examiner without knowledge of the clinical findings. Two children with evidence of borderline RHD were re-examined at B.P. Koirala Institute of Health Sciences and the indication for secondary antibiotic prevention was discussed with the parents and the children. At 6 months of follow-up, echocardiographic findings were stable in both children. Implementation of secondary antibiotic prevention was challenged by impaired awareness of subclinical RHD among parents and inadequate cooperation with family physicians. CONCLUSIONS: This pilot study shows that the methods outlined in the protocol can be translated into a large-scale population-based study. We learned that education and collaboration with teachers, parents and family physicians/paediatricians will be of key importance in order to establish a sustainable programme.

Rheumatic heart disease revisited: patterns of valvular involvement from a consecutive cohort in eastern Nepal.

BACKGROUND: The burden of rheumatic heart disease (RHD) continues to be a major contributor to morbidity and premature death in poor and developing countries. We investigated patterns of valvular involvement in patients with RHD as observed in a large tertiary care hospital in eastern Nepal. METHODS: We retrospectively reviewed transthoracic echocardiography reports from patients diagnosed with RHD between June 1999 and February 2011. RESULTS: Among 10 860 transthoracic echocardiography studies, 1055 female and 658 male patients were diagnosed with RHD, 25.7% of the patients being below 20 years of age. Mitral regurgitation was the most common valvular lesion across all age groups irrespective of sex (n = 1321, 77.1%). Female patients were significantly older as compared to male patients at the time of presentation (32.8 ±â€Š15.2 versus 28.5 ±â€Š15.4 years; P < 0.001) and more commonly presented with mitral stenosis as compared to male patients (62.8 versus 51.5%; P < 0.001), with a peak between the age of 30 and 49 years. Conversely, aortic regurgitation was more common in men as compared to women (55.6 versus 48.9%; P = 0.007). Involvement of both the mitral and the aortic valve was observed in 49.8% of the patients and was more common in men as compared to women (52.7 versus 47.8%; P = 0.047). CONCLUSION: In this consecutive cohort of patients with RHD in Nepal differential patterns of valvular involvement are observed across sex and age categories.

Protocol for a population-based study of rheumatic heart disease prevalence and cardiovascular outcomes among schoolchildren in Nepal.

INTRODUCTION: Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established. METHODS AND ANALYSIS: The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries. ETHICS AND DISSEMINATION: The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with http://www.ClinicalTrials.gov (NCT01550068). The study findings will be reported in peer-reviewed publications. CLINICALTRIALS.GOV IDENTIFIER: NCT01550068.

Double-vessel coronary stenting via 5 French diagnostic catheters.

The authors report on the use of 5 French diagnostic catheters to deliver a stent-on-a-wire system during a double vessel coronary intervention.

Prevalence of hypertension, obesity, diabetes, and metabolic syndrome in Nepal.

Background. This study was carried out to establish the prevalence of cardiovascular risks such as hypertension, obesity, and diabetes in Eastern Nepal. This study also establishes the prevalence of metabolic syndrome (MS) and its relationships to these cardiovascular risk factors and lifestyle. Methods. 14,425 subjects aged 20-100 (mean 41.4 ± 15.1) were screened with a physical examination and blood tests. Both the International Diabetic Federation (IDF) and National Cholesterol Education Programme's (NCEP) definitions for MS were used and compared. Results. 34% of the participants had hypertension, and 6.3% were diabetic. 28% were overweight, and 32% were obese. 22.5% of the participants had metabolic syndrome based on IDF criteria and 20.7% according to the NCEP definition. Prevalence was higher in the less educated, people working at home, and females. There was no significant correlation between the participants' lifestyle factors and the prevalence of MS. Conclusion. The high incidence of dyslipidemia and abdominal obesity could be the major contributors to MS in Nepal. Education also appears to be related to the prevalence of MS. This study confirms the need to initiate appropriate treatment options for a condition which is highly prevalent in Eastern Nepal.